On 27 August 2012, both the US Food and Drug Administration (FDA) and Gilead Sciences issued news releases confirming the approval for a single pill boosted integrase inhibitor fixed dose combination for adult HIV treatment.
Developed under the name Quad and with a new tradename Stribild, the combination contains elvitegravir, a new pharmacokinetic booster called cobicistat, FTC and tenofovir. The indication is for treatment-naive patients with estimated creatinine clearance (CrCl) of >70 mL/min.1,2
The two large phase 3 studies on which approval was based compared Quad to Atripla (efavirenz/FTC/tenofovir) and to atazanavir/ritonavir plus separate FTC/tenofovir. Both studies concluded that Stribild was non-inferior to the comparitor arms with 88-90% rates of undetectable viral load at week 48 compared to 84% with Atripla and 87% with boosted atazanavir.
Stribild needs to be taken with food. This is based on increased mean exposure of elvitegravir and tenofovir by 34% and 24% respectively with a light meal (373 kcal, 20% fat) and by 83% and 23% respectively with a higher fat meal (~800 kcal, 50% fat).3
Of note, the US DHHS guidelines have already issued an update that recommends Stribild as an alternative rather than preferred option for first-line therapy. This decision was based on "a significant potential for drug-drug interactions, the availability of only 48 weeks of safety data, usage limited to individuals with pre-treatment CrCl >70 mL/min, a possible increased risk of proximal renal tubulopathy, limited data in patients with advanced HIV disease and in women, and the need for the drug to be taken with food".4
But the expected welcome for an important new option for treatment is tempered by a US price more than a third higher than Atripla (approximately $28,500 vs $21,000 for the US annual wholesale list price). Although the European decision on approval is not expected until later this year, and drug pricing is complex, a similar differential in the UK would severely restrict prescribing.7
While Quad offers potential advantages to some current options, these were not demonstrated in the clinical trials that led to approval based on finding it is "not likely to be worse" than current treatment, based on a non significant 4% difference in the percentage of patients with undetectable viral load after 48 weeks of treatment.
Unless Stribild is a cost neutral option compared to Atripla, this potentially important new drug is likely to be rarely used in the UK. Without a cost-neutral price compared to boosted atazanavir or boosted darunavir, it is likely to be rarely used in second-line therapy, or as a switch option based on a better side effect profile compared to efavirenz. If the price is not cost-neutral compared to raltegravir, it is unlikely to be widely used in patients with multidrug resistance.
The cost differences are likely to widen further when efavirenz comes off patent in 2013, with costs savings from generic formulations expected to be sufficient to routinely switch patients from Atripla to efavirenz and separate tenofovir/FTC.
While switching between brand and generic formulations is a basic tenet of NHS healthcare, switching between classes is not.
Gilead have stated that this is a competitive price for the US market and that they have set up patient access programme. Gilead in the UK do not want to comment on European pricing prior to EU licensing.
No comments have been made.